The effects of caffeine and caffeine withdrawal on mood, cognition, and fMRI.

描述（由申请人提供）：咖啡因是一种广泛使用的神经兴奋剂，存在于许多食品和饮料中，如咖啡、茶、软饮料和巧克力。它的高使用率很重要，因为咖啡因对情绪、认知表现和生理指标有急性和慢性影响。咖啡因非选择性地拮抗腺苷受体，从而作为神经兴奋剂和血管收缩剂。咖啡因能改善情绪和注意力，减少静息时脑血流量。然而，长期摄入咖啡因会导致腺苷受体的上调。在长期使用者中，有证据表明对神经刺激作用产生耐受性，并且在咖啡因戒断期间出现头痛和疲劳等戒断症状。事实上，有人提出，咖啡因的戒断效应的逆转超过了咖啡因长期使用者的任何急性净收益。这一建议一直存在争议，因为行为学文献中存在差异，对咖啡因和咖啡因戒断的影响进行更全面的调查是有必要的。最近，人们利用功能磁共振成像（fMRI）研究了咖啡因的作用。然而，通过拮抗血管腺苷受体，咖啡因干扰神经活动和血流动力学反应之间的耦合。这可能会降低血氧水平依赖（BOLD）信号的峰值幅度，这与咖啡因的神经刺激作用不一致。这个问题可以通过测量BOLD信号的时间过程参数来避免，因为有证据表明咖啡因减少了神经对刺激反应的潜伏期。拟议的研究将利用情绪、认知表现和生理学的测量来研究咖啡因在天然咖啡因状态和戒掉咖啡因30小时后的戒断状态下的影响。该项目的具体目标将确定状态和药物对1)情绪和认知表现的测量，2)BOLD信号的时间过程参数，以及3)行为表现与BOLD信号的时间过程参数之间的关系。

DESCRIPTION (provided by applicant): Caffeine is a widely used neurostimulant that is found in many foods and beverages such as coffee, tea, soft drinks, and chocolate. Its high incidence of use is significant because caffeine has both acute and chronic effects on measures of mood, cognitive performance, and physiology. Caffeine nonselectively antagonizes adenosine receptors, thereby acting as both a neurostimulant and vasoconstrictor. Acutely, caffeine improves mood and attention, and reduces resting cerebral blood flow. However, chronic caffeine use results in an upregulation of adenosine receptors. Among chronic users there is evidence that tolerance develops to the neurostimulant effects, and withdrawal symptoms such as headache and fatigue appear during caffeine abstinence. In fact, it has been proposed the reversal of the withdrawal effects outweighs any acute net benefits of caffeine in chronic users. This proposal has been debated because discrepancies exist in the behavioral literature and a more comprehensive investigation of the effects of caffeine and caffeine withdrawal is warranted. Recently, the effects of caffeine have been studied using functional magnetic resonance imaging (fMRI). However, by antagonizing vascular adenosine receptors, caffeine interferes with the coupling between neural activity and the hemodynamic response. This may reduce the peak amplitude of the blood oxygenation level dependent (BOLD) signal, inconsistent with the neurostimulant effects of caffeine. This issue may be avoided by measuring time course parameters of the BOLD signal instead, since evidence suggests that caffeine decreases the latency of a neural response to a stimulus. The proposed study will address this by utilizing measures of mood, cognitive performance, and physiology to investigate the effects of caffeine in a native caffeinated state and a withdrawal state following 30 hours of caffeine abstinence. The specific aims for this project will determine the state and drug effects on 1) measures of mood and cognitive performance, 2) time course parameters of the BOLD signal, and 3) the relationship between behavioral performance and time course parameters of the BOLD signal. PUBLIC HEALTH RELEVANCE: Caffeine is an excellent model drug because it is safe to administer and has a low abuse liability, yet chronic use will result in tolerance and withdrawal symptoms similar to drugs of abuse. As a model drug, caffeine could add to our understanding of how the avoidance of withdrawal symptoms contributes to the reinforcing effects of drugs. The issues addressed in this proposed study are pertinent to all neuroactive drugs that simultaneously affect cerebral blood flow. The information gained from this study will improve our understanding of caffeine and will lend itself to the study of other drugs using pharmacological fMRI.